Apparatus for preparing gels for use in electrophoretic separations and similar applications

ABSTRACT

An apparatus for the rapid preparation of electrophoresis gels comprises: (a) a housing; (b) a support fixture removably disposed within the housing and adapted to receive a gel holder having an internal gel compartment, the support fixture being optionally adapted to permit filling of the gel holder within the housing; (c) an optional injection system, which is connectible to a reservoir for holding a polymerizable solution; (d) an optional solution injection connector adapted to couple the injection system to a gel holder placed within the filling fixture, (e) an optional controller for the injection system, which causes the injection system to inject polymerizable solution from the reservoir into the gel compartment; and (f) a radiation source disposed within the housing in a location effective to irradiate polymierizable solution within the gel compartment of a gel holder in the support fixture. The support fixture may be mounted on a drawer which is slidable between a position inside the housing, and a position outside the housing to permit easy placement of a gel holder into the support fixture.

This application is a continuation-in-part of U.S. patent applicationSer. No. 332,892 filed Nov. 1, 1994, now U.S. Pat. No. 5,507,934.

I. BACKGROUND OF THE INVENTION

This application relates to an apparatus for preparing gels particularlypolyaciylamide gels, for use in electrophoretic separation ofbiomolecules and similar applications.

Polyacrylamide gel electrophoresis (PAGE) separation of biomolecules isnow routinely performed. Current Protocols in Molecular Biology, Chap.10, John Wiley & Sons, (1994). A polyacrylamide gel provides a suitablyinsoluble sieve that separates biomolecules in solution by size andconformation as they are drawn through the sieve under electromotiveforce. Such separation of biomolecules provides valuable insights intotheir structures and functions. For example, PAGE separation canseparate two polypeptides of the same size but of different isoforms orpolypeptides only 100 daltons difference in size (Current Protocols,1994). Another use for PAGE is in separation of nucleic acids based onsize of fragments, such as in the extremely important application of DNAsequence determination. Maniatis et al., Molecular Cloning: A LaboratoryManual, 2nd ed., Chap. 13 (1987).

The prior art on PAGE is extensive. Many patents and scientific papersdisclose uses for PAGE in research applications. DNA sequencing may becarried out using automated systems designed for laboratory application.These techniques have historically been important for sequencing longstretches of unknown DNA, such as is the focus of the Human GenomeProject. Methods and apparatus for sequencing of DNA are described inU.S. Pat. Nos. 4,811,218; 4,823,007; 5,062,942; 5,091,652; 5,119,316;5,122,345; 5,228,971, and 5,338,426 which are incorporated herein byreference.

Unfortunately, the traditional techniques for preparation of gels foruse in electrophoresis are inadequate for use in clinical diagnosticservices, such as the emerging field of clinical diagnostic DNAsequencing. For clinical diagnostic DNA sequencing purposes, it isdesirable to sequence hundreds of DNA sequences per day. Existingmethods do not provide for such capacity. For example, typical methodsof DNA sequencing require that a skilled technician spend up to fourhours constructing a gel holder, filling the gel holder with activelypolymerizing acrylamide solution, inserting a well-forming comb beforesubstantial polymerization has occurred, and then waiting for the gel topolymerize. (U.S. Pat. Nos. 5,338,426; 5,069,773; Maniatis, 1987). Usingthe gel is equally cumbersome. Loading sample to be electrophoresedrequires painstaking care to ensure the integrity of loading wells andto prevent samples from running together. Thus, in order to make maximumclinical use of the opportunities presented by our ever increasing,knowledge of the human genetics and the genetic causes of many disease,it would be advantageous to have a method of rapidly makingpolyacrylamide gels which are convenient for more efficient sampleloading and running, particularly for use in clinical diagnosticapplications.

It is an object of the invention to provide an apparatus for filling agel holder with a polymerizable solution, and catalyzing thepolymerization of the solution using ultraviolet light to form a gelusable for electrophoretic separation of biomolecules, particularlynucleic acids.

It is a further object of the invention to provide a cartridge for useas a reservoir in the gel filling and polymerizing apparatus of theinvention.

It is a further object of the invention to provide an apparatus forpolymerizing an already filled gel holder.

It is a further object of the invention to provide a method forpreparing an electrophoresis gel which uses the apparatus of theinvention.

It is a further object of the invention to provide an apparatus for therapid and convenient formation of gels which are more easily loaded withsample.

II. SUMMARY OF THE INVENTION

These and other objects are achieved using an apparatus specificallydesigned for the rapid filling and polymerization of electrophoresisgels. This apparatus comprises:

(a) a housing;

(b) a filling fixture removably disposed within the housing and adaptedto receive a gel holder having an internal gel compartment;

(c) an injection systems which is connectible to a reservoir for holdinga polymerizable solution;

(d) a solution injection connector adapted to couple the injectionsystem to a gel holder placed within the filling fixture,

(e) a controller for the injection system, which causes the injectionsystem to inject polymerizable solution from the reservoir into the gelcompartment; and

(f) a radiation source disposed within the housing in a locationeffective to irradiate polymerizable solution within the gel compartmentof a gel holder in the filling fixture. In a preferred embodiment of theapparatus, the filling fixture is mounted on a base which is slidablebetween a position inside the housing and a position outside the housingto permit easy placement of a gel holder into the filling fixture.

III. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a gel holder which may be filled and polymerized using themethod and apparatus of the invention;

FIG. 2 shows an exterior view of an apparatus according to theinvention;

FIGS. 3A and B shows a filling fixture for use in accordance with theinvention;

FIG. 4 shows a side sectional view of a filling fixture for use inaccordance with the invention having a gel holder positioned therein;

FIG. 5 shows a detailed view of the connection between the injectionsystem and the gel holder;

FIG. 6 shows a cross-sectional view of an embodiment of the invention;

FIG. 7 is a cross-section through a disposable cartridge useful as areservoir for polymerizable solution;

FIG. 8 shows a gel polymerization apparatus according to the invention;and

FIG. 9 shows a top view of a gel holder for use in accordance with theinvention.

IV. DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an apparatus for the filling of apre-formed gel holder, and for the polymerization of the gel within theholder. Preferred gel holders are those described in commonly assignedU.S. patent application Ser. No. 08/332,557 and the PCT Application No.PCT/US95/14531 (WO96/13717)being concurrently filed herewith which is acontinuation-in-part of said U.S. application, which applications areincorporated herein by reference. As shown in FIG. 1, such gel-holders10 generally comprise a top substrate 11, a bottom substrate 12, andmeans 13 for scaling the top substrate 11 to the bottom substrate 12 toform a gel compartment having a thickness of 250 microns or less. Themeans 13 for sealing has an opening therethrough for filling the gelcompartment with an unpolymerized gel. The means for sealing may takethe form of an adhesive applied between the top and bottom substratesalong at least two opposing edges of the top and bottom substrates.

The separation between the two substrates, and thus the size of the gelcompartment is advantageously defined and maintained using a spacer. Oneform which the spacer may take is a plurality of solid particlesdisposed between the top and bottom substrate and having a mean diametersubstantially equal to the thickness of the gel compartment.Advantageously, at least a portion of these particles are disposedwithin the adhesive.

Suitable adhesives for use in such gel holders are acrylatc adhesives.In some cases, however, there may be an interference between materialsin the adhesive and the subsequent polymerization of the gel. For thisreason, it may be preferable to affix the solid particles to the top orbottom substrate by forming a mixture of a powder of a low melting glasswith a plurality of the solid particles; dispersing the mixture on asurface of the substrate for example by screen printing; heating thesubstrate and mixture to melt the low melting glass powder; and coolingthe heated substrate to resolidify the low melting glass, whereby a bondbetween the solid particles and the substrate is formed.

FIG. 2 shows an exterior view of an apparatus in accordance with theinvention. As indicated, the apparatus is disposed within a housing 20.Inside the housing is a radiation source such as an ultraviolet lamp orbank of lamps for use in initiating polymerization of the gel.Preferably, the radiation source is positioned so that the totalradiation received by any one part of the gel holder is the same as anyother. If a number of identical lamps are used, this may require thatthe lamps be spaced more closely together at the edges than at thecenter of the gel.

A control panel 21 and a sliding drawer unit 22 are positioned on afront face of the housing 20. Tracks 23 are attached at on sides of thedrawer unit 22. The tracks 23 fit into sliding track guides 24 (shown inphantom in FIG. 2) mounted on each side inside the housing 20. At itsfull extension, the sliding tracks 23 are retained in the sliding trackguides 24 by track stops (not shown). At its full retraction the slidingof the drawer is stopped by contact of the face 25 of the drawer withthe housing 20. Any sliding means with low coefficient of friction maybe employed to bear the weight of the drawer, such as ball bearings,Teflon, wheels or rubber.

The drawer unit 22 supports a filling fixture 30 such as that shown inFIGS. 3A, 3B and 4. The filling fixture 30 has a rectangular frame 31surrounding a central base region 32 sized to receive a gel holder. Thegel holder rests over the central base region 32 and is supportedunderneath along each side by a narrow (˜3 mm) ledge 33 protruding fromthe filling fixture. Alternatively, the gel holder 10 may be supportedby and held between support members 43 running across the central baseregion 32 as shown in FIG. 4.

When first placed in the filling fixture, the open end of the microgelholder loosely contacts a silicon strip 34 at the bottom of the fillingfixture 30. At the top of the filling fixture, a silicon strip 35attached to an adjustable bar 36 running widthwise at the top of thefilling fixture 30 loosely contacts the top end of the gel holder. Bymeans of a screw 37 or other force directing means, such as a lever, thesilicon strip 35 on the moveable bar 36 is placed in close contact withthe top of the gel holder and the bottom of the gel holder is therebysecured in close, sealing contact with the silicon strips 34 and 35 atthe bottom and top of the filling fixture 30. Fixed guide bolts 38 whichslide within openings in the frame 31 ensure that the moveable bar 36 isstabilized and directed smoothly in the direction of the force of thescrew 37.

The bottom end of the filling fixture 30 and the silicon strip 34 havean injection port 39 passing through them. When the gel holder isproperly secured in the filling fixture 30, the injection port 39 isaligned with the open bottom edge of the gel holder 10 as shown in FIG.5, providing a pathway for injection of a polymerizable solution intothe gel compartment 13 of the gel holder 10. Thus, the silicon strip 34serves as a solution injection connector and is adapted to couple theinjection system to a gel holder placed within the filling fixture.

When the microgel holder is secured in the filling fixture it is readyto be filled and polymerized. Filling and polymerization takes placeinside the housing 20. The drawer unit 22 containing gel holder 10, inthe filling fixture 30, is slid inwards into the housing 20. In apreferred embodiment of the invention, closing the drawer starts anautomated filling and curing process in which polymerizable solution ispumped into the gel holder, and an ultraviolet light disposed within thehousing 20 over the gel holder is activated to initiate thepolymerization reaction.

FIG. 6 shows a cross-sectional view of one embodiment of the inventionin which a two level drawer unit 220 is utilized. As shown, the fillingfixture 30 with the gel holder disposed therein is disposed on the uppershelf 61 of the drawer unit 220. A lower shelf 62 supports the solutioninjection system which is connected to the solution injection port ofthe top shelf by a tube 72.

The solution injection system comprises a canister 63 of gel formingsolution. The solution employed may be an acrylamide solution, with orwithout urea or sodium dodecyl sulphate (SDS), and with or without anyother chemical additives, alternatively it may be any non-acrylamidemonomer which exists in solution at or around room temperature and canbe polymerized in the presence of ultraviolet light, either with orwithout further additives.

The canister 63 contains a plunger 64 operatively connected to a motor65. When the motor is activated, the plunger 64 is driven by thededicated motor 65 for a predetermined period of time to dispense thecorrect amount of gel forming solution into the gel holder. In addition,fan 70 may be turned on at the motor to provide venting and heatdissipation inside the housing as part of the process of starting thefilling and polymerization cycle, or it may be activated separately.

The injected solution flows evenly through the gel compartment, fillingthe compartment. Air escapes from the gel compartment through theopenings in the window of the top substrate. After the gel compartmenthas been filled, UV lamps 66 disposed in the top of the housing areactivated for a period of time sufficient to polymerize the gel in theholder. For example, using five 20 Watt UVA lamps an acrylamide solutionin a gel holder will be fully polymerized in about 5 to 10 minutes. Theapparatus then shuts off the lamps and signals completion of the cycle,for example by opening the drawer unit, by sounding an audible alarm orby lighting a signal light.

Activation of the motor 65 to start the gel filling and polymerizationcycle can be accomplished by any of several means. First, the cycle canbe initiated in response to a command or series of commands enteredthrough the control panel 21 on the front of the housing 20, or theactivation of a "start" switch. In the simplest embodiment of theinvention, each phase of the processing is started separately by anoperator. Thus, a command is entered to start the filling process, andthen a second command is entered after the filling process is completeto energize the lamps inside the housing and begin the polymerizationpart of the cycle.

Preferably, the apparatus will include a mechanism for the controllingthe performance of a complete filling and polymerization cycle inresponse to a single initiation signal. Thus, for example, the apparatusmay include a user interface circuit board ("UI Circuit Board") whichautomatically coordinates the filling/polymerization cycle. The UICircuit Board is connected to a microprocessor which controls the motor65 for gel filling, and the illumination of the ultraviolet lamps 66.Upon activation of a switch on the UT Circuit Board, the microprocessoractivates the motor 65 for a predetermined but adjustable period oftime. The adjustment of this time interval may be presented to the useras a time interval or as an adjustment in the volume of polymerizablesolution to be transferred. The motor 65 is then turned off by themicroprocessor, and the lamps 66 are energized for a predetermined butuser adjustable period of time.

The UI Circuit Board may contain a further switch or switches forcontrolling the motor 65. A first such switch would allow forreplacement of the canister 63 by fully retracting the plunger 64 fromthe canister. A second switch could allow for manual control of themotor 65, for example to permit priming of the solution injection systemafter replacement of the canister 63.

As an alternative to the use of a switch on the exterior of the housing,a filling/polymerization cycle can be started automatically upon closureof the drawer unit. For example, a switch may be placed such that it isautomatically actuated when the drawer unit is closed. In this case, itis advantageous to place an sensor switch in the filling fixture 30 suchthat the mechanism can only operate when a gel holder is installed inthe fixture.

The apparatus shown in FIG. 6 further shows a reversible belt 67attached to the drawer unit 22. The belt 67 is supported by a driven andan undriven pulley 68 and 68'. The driven pulley 68 is connected tomotor 69, which in turn is connected to a switch 71 on the front of thehousing. The motor 69 extends the drawer or retracts the drawer inresponse to the position of switch 71. The activation of this switch toretract the drawer may also initiate the filling/polymerization cycle.

While the invention has been described with above with reference to theformation of polyacrylamide gels cross-linked using ultra-violet lightas an initiator, it will be understood that the invention can also beused with other initiator systems and radiation sources. For example,polymerization of 2-10% (w/v) acrylamide, 19:1 bisacrylamide can beinitiated using a radiation source at a wavelength of 450 nm in thepresence of 100 μM methylene blue, 1 mM sodium toluenesulfinate and 50μM diphenyliodonium chloride. Similarly, if the cross-linking isachieved with a thermal initiator such as TEMED, IR lamps may be used asthe radiation source 66.

After polymerization, the polymerized microgel in the microgel holder isremoved from the filling fixture by unscrewing or unclamping themicrogel holder. The microgel is now ready to be mounted on a gelrunning apparatus and loaded with sample to be electrophoresed on thegel.

The apparatus of the present invention is advantageously constructed toutilize a disposable cartridge containing polymerization monomers orprepolymers of the type shown in FIG. 7. The cartridge is formed from ahollow body member 171, having an interior cavity 172 with substantiallyconstant cross-section from a first end A to a point B near an opposingsecond end, providing a volume of from 5-500 ml, preferably about 50 ml.The interior cavity 172 is tapered at the second end to form adispensing orifice 173. A slidable plug 174 is sized to tightly slidewithin the interior cavity 172 in the region of constant cross sectionand is placed in within a first end of the hollow body member. A capmember 175 for sealing the dispensing orifice 173 is also provided.

Gel forming monomers or prepolymers 176 are disposed within the interiorcavity 172, optionally separated from a polymerization initiator 177 bya rupturable seal 178. Preferred gel-forming monomers are acrylamidemonomers. Preferred initiators are photopolymerization initiators suchas riboflavin or methylene blue.

To fill the cartridges, gel forming materials and polymerizationinitiators are placed in the interior cavity 172. The plug is theninserted in the wide end of the cartridge. Air is forced out of thecartridge through the dispensing orifice by pressing in on the pluguntil the gel forming material has displaced all of the air. Thedispensing orifice is then capped, for example with a screw-on cap. Thewide end may then be covered over with a protective cap (not shown) toinsure no movement of the plug during shipment.

When use is required, the cap on the dispensing orifice is removed, anda narrow gauge (i.e., 0.5 to 5 mm diameter) flexible hose (of rubber orsilicon or the like) is attached to the narrow end. A luer fitting maybe employed to improve the attachment. The opposite end of the hose isconnected, preferably with a luer fitting, to the filling bore in thefilling fixture manifold. In an alternative format, the hose may beattached to the plug before shipment, and only the distal end of thehose requires connection to the filling bore.

Once the hose is connected, the protective cap of the cartridge isremoved, exposing the plug. The prepared cartridge may then be placed inan automated or manual system for the filling of gel cassettes. In amanual system, the prepared cartridge is connected with a snapconnection directly to a filling gun such as the DispensGun (TM)(Specialty Products, East Providence, R.I.). The plunger in the gun isadjusted to contact the plug. With each squeeze of the gun's trigger theplunger of the gun drives the plug into the cartridge. The gel formingsolution is driven out of the cartridge, through the hose, into thefilling fixture bore, and eventually into the cassette.

An automated system uses an automatic dispensing motor which drives theplug into the cartridge at a push of a button. Such automatic dispensingis advantageous in that less variation in solution flow is introduced byhuman operators.

Cartridges for use with chemically induced polymerization, such asAPS/TEMED gels, can also be constructed using a separate barrel-typesyringe attached to the side of the main cartridge, or using a cartridgewhich is divided into two chambers. One chamber is filled with gelforming solution, while the other chamber is filled with a catalystwhich hastens polymerization of the gel forming solution. An injectiongun with a double pronged plunger is used to inject the correct amountof solutions into a static mixing chamber just above the needle of thecartridge. The mixed solution is driven into the gel cassette by theaction of the plungers where it polymerizes.

While the fully automated filling and polymerizing apparatus describedabove provides for substantial benefits including increased throughputand reliability in the production of electrophoresis gels, in some casesit may be desired to pre-fill the gel holder with unpolymerizedmaterial. Thus, as shown in FIG. 8, a further aspect of the inventionprovides a gel polymerization apparatus comprising a housing 381 and adrawer 361. The drawer 361 is slidably disposed with the housing 381,and is movable between an extended position and a retracted position.The drawer 361 and said housing 381 together form a light tightenclosure when the drawer 361 is in the retracted position. A removablesupport fixture 30 may be disposed within the drawer 361. The supportfixture 30 is adapted to receive a gel holder, and may be substantiallyidentical to the filling fixture described above. Of course, the supportfixture need not include means for introducing a polymerizable solutioninto the gel compartment. Finally, there is a radiation source 66disposed within the housing in a location effective to irradiatepolymerizable solution within the gel compartment of a gel holder in thesupport fixture. As in the case of the fully automated gel filling andpolymerizing apparatus, the lamps may provide ultraviolet, visible or IRradiation depending on the nature of the materials to be polymerized.The apparatus may also include a motor and control devices as in theapparatus shown in FIG. 6.

When a polymerization-only apparatus is used, the gel holder is filledwith polymerizable solution outside the apparatus. This can be donemanually using a syringe, or manual dispensing gun such as theDispensGun™ available from Specialty Products, East Providence, R.I., orusing a motorized plunger of the same type generally employed in thefully automated apparatus. The latter technique is preferred since itreduces variability caused by the operator. Once filled, the gel holdersshould be promptly transferred to the polymerization apparatus to avoidsignificant room-light induced polymerization which may be unevenleading to a less than desirable gel.

The use of a polymerization-only apparatus may be particularly effectiveon forming gels within microgel holders of the type described in U.S.patent application Ser. No. 08/332,557, and the concurrently filed PCTapplication which is a continuation in part thereof. Thus, a furtheraspect of the present invention is a method of preparing anelectrophoresis gel comprising the steps of:

(a) filling a gel holder with a gel-forming solution, said gel holdercomprising a top substrate, a bottom substrate, and means for scalingthe top substrate to the bottom substrate to form a gel compartmenthaving a thickness of 250 microns or less, said means for sealing havingan opening therethrough for filling the gel compartment with anunpolymerized gel;

(b) placing the filled gel holder in a polymerization apparatuscomprising a housing, a drawer slidably disposed with the housing, saiddrawer being movable between an extended position and a retractedposition, and said drawer and said housing together forming a lighttight enclosure when the drawer is in the retracted position, and aradiation source disposed within the housing in a location effective toirradiate polymerizable solution within the gel compartment of a gelholder in the support fixture, said radiation source providingsubstantially equal amounts of radiation to all parts of the gel holder,said gel holder being placed on the drawer when it is in the extendedposition;

(c) placing the drawer of the polymerization apparatus in the retractedposition, whereby the gel holder is enclosed the light tight enclosure;and

(d) irradiating the filled gel holder within the light tight enclosurefor a period of time sufficient to polymerize the gel-forming solution.The separation between the two substrates in the gel holder may bedefined by a plurality of solid particles, as described in theabove-mentioned applications, although other means to maintain thespacing may also be used.

EXAMPLE

A UV activated adhesive matrix was prepared using Minico® M07950-Racrylate adhesive from Emerson & Cuming Inc., Woburnm Mass., mixed with2% by weight Sigma® glass beads (106 micron and finer) filtered toselect beads of a size of 45 to 53 microns. The adhesive matrix wasscreen printed onto the bottom substrate 12 in the pattern shown in FIG.9. The top substrate 11 was then positioned on top of the bottomsubstrate 12. The substrates were then exposed to 20 Watts UVA light(wavelength 315-385 nm) to initiate curing of the adhesive and to bondthe two substrates together.

After the adhesive was cured, the gel holder was placed horizontally ina filling fixture in accordance with the invention and placed into thetop shelf of a device as shown in FIG. 6. A first switch on the UICircuit Board was manually activated which initiated retraction of thedrawer into the housing. Upon full retraction of the drawer, a secondswitch on the UI Circuit Board was manually activated to commence thefilling/polymerization cycle. A polyacrylamide gel forming solutioncontaining 6% acrylamide (19:1 bis-acrylamide), 7 M urea in 0.6×TBE and10 ppm riboflavin was driven into the gel holder, which was then exposedto ultraviolet light from five 20 W UVA-lamps disposed on the interiorof the housing for 10 minutes to polymerize the gel.

We claim:
 1. An apparatus for polymerizing a gel, comprising(a) ahousing; (b) an injection system, said injection system connectible to areservoir for holding a polymerizable solution; (c) a filling fixtureremovably disposed within the housing and adapted to receive a gelholder having an internal gel compartment; (d) a solution injectionconnector adapted to couple the injection system to the internal gelcompartment of a gel holder placed within the filling fixture, (e) acontroller for the injection system, which causes the injection systemto inject polymerizable solution from the reservoir directly into thegel compartment without filling the remainder of the housing; (f) aradiation source disposed within the housing in a location effective toirradiate polymerizable solution within the gel compartment of a gelholder in the filling fixture, and (g) a reservoir connected to theinjection system, wherein the reservoir is a cartridge comprisingahollow body member having an interior cavity with substantially constantcross-section from a first end to a point near an opposing second end,said cavity being tapered at the second end to form a dispensingorifice; a slidable plug sized to tightly slide within the interiorcavity in the region of constant cross section, said plug being disposedwithin a first end of the hollow body member; gel forming monomers orprepolymers disposed within the interior cavity; and a polymerizationinitiator disposed within the interior cavity.
 2. An apparatus accordingto claim 1, wherein the controller is connected to a switch, and whereinactivation of the switch initiates a cycle of filling the gel holderwith polymerizable solution and irradiating the gel holder to polymerizethe polymerizable solution.
 3. An apparatus according to claim 1,wherein the filling fixture is disposed on a drawer slidably disposedwithin the housing.
 4. All apparatus according to claim 3, wherein thedrawer has an upper shelf and a lower shelf, and wherein the fillingfixture is disposed on the upper shelf and the injection system isdisposed on the lower shelf.
 5. An apparatus according to claim 4,wherein the reservior of the injection system is disposed on the lowershelf.
 6. An apparatus according to claim 4, further comprising a motoroperatively connected to the drawer for retracting and extending thedrawer.
 7. An apparatus according to claim 6, wherein the controller isconnected to a switch, and wherein activation of the switch initiates acycle of filling the gel holder with polymerizable solution andirradiating the gel holder to polymerize the polymerizable solution, andcauses the drawer to be retracted into the housing at the beginning ofthe cycle and extended from the housing at the end of the cycle.
 8. Anapparatus according to claim 1, wherein the radiation source irradiatesthe polymerizable solution with ultraviolet radiation.
 9. An apparatusfor polymerizing a gel, comprising(a) a housing; (b) a drawer slidablydisposed with the housing, said drawer being movable between an extendedposition and a retracted position, and said drawer and said housingtogether forming a light tight enclosure when the drawer is in theretracted position; (c) a support fixture removably disposed within thedrawer and adapted to receive a gel holder having an internal gelcompartment containing a polymerizable solution; and (d) a radiationsource disposed within the housing in a location effective to irradiatepolymerizable solution within the gel compartment of a gel holder in thesupport fixture, said radiation source providing substantially equalamounts of radiation to all parts of the gel holder.
 10. An apparatusaccording to claim 9, wherein the radiation source comprises a pluralityof individual lamps.
 11. An apparatus according to claim 10, wherein thelamps are ultra-violet lamps.
 12. An apparatus according to claim 10,wherein the lamps provide radiation at a wavelength of 450 nm.
 13. Amethod of preparing an electrophoresis gel comprising the steps of:(a)filling a gel holder with a gel-forming solution, said gel holdercomprising a top substrate, a bottom substrate, and means for scalingthe top substrate to the bottom substrate to form a gel compartmenthaving a thickness of 250 microns or less, said means for scaling havingan opening therethrough for filling the gel compartment with anunpolymerized gel; (b) placing the filled gel holder in a polymerizationapparatus comprising a housing, a drawer slidably disposed with thehousing, said drawer being movable between an extended position and aretracted position, and said drawer and said housing together forming alight tight enclosure when the drawer is in the retracted position, anda radiation source disposed within the housing in a location effectiveto irradiate polymerizable solution within the gel compartment of a gelholder in the support fixture, said radiation source providingsubstantially equal amounts of radiation to all parts of the gel holder,said gel holder being placed on the drawer when it is in the extendedposition; (c) placing the drawer of the polymerization apparatus in theretracted position, whereby the gel holder is enclosed the light tightenclosure; and (d) irradiating the filled gel holder within the lighttight enclosure for a period of time sufficient to polymerize thegel-forming solution.
 14. The method according to claim 13, wherein thegel-forming solution comprises acrylamide monomers and a photoinitiator.15. The method according to claim 14, wherein the photoinitiator ismethylene blue.
 16. The method according to claim 14, wherein thephotoinitiator is riboflavin.
 17. A method according to claim 13,wherein the means for sealing the substrates comprises an adhesiveapplied between the top and bottom substrates along at least twoopposing edges of the top and bottom substrates.
 18. The methodaccording to claim 17, wherein the gel holder further comprises aplurality of solid particles, said solid particles being disposedbetween the top and bottom substrate and having a mean diametersubstantially equal to the thickness of the gel compartment, and atleast a portion of the particles are disposed within the adhesive. 19.The method according to claim 13, wherein the gel holder furthercomprises a plurality of solid particles, said solid particles beingdisposed between the top and bottom substrate and having a mean diametersubstantially equal to the thickness of the gel compartment.
 20. Themethod according to claim 19, wherein at least a portion of the solidparticle are affixed to the top or bottom substrate by the steps offorming a mixture of a powder of a low melting glass with a plurality ofthe solid particles; dispersing the mixture on a surface of thesubstrate; heating the substrate and mixture to melt the low meltingglass powder; and cooling the heated substrate to resolidify the lowmelting glass, whereby a bond between the solid particles and thesubstrate is formed.